Methyl benzoate, formation

The addition of methanol decreases the rate of the esterification of carboxylic acids with DMC-DBU. Without the added methanol methyl benzoate 2 is quantitatively obtained within 3 h, but with extra methanol added, methyl benzoate formation is still not complete after 24 h. Could you explain why ... 

Mix 31 g. (29-5 ml.) of benzyl alcohol (Section IV, 123 and Section IV,200) and 45 g. (43 ml.) of glacial acetic acid in a 500 ml. round-bottomed flask introduce 1 ml. of concentrated sulphuric acid and a few fragments of porous pot. Attach a reflux condenser to the flask and boil the mixture gently for 9 hours. Pour the reaction mixture into about 200 ml. of water contained in a separatory funnel, add 10 ml. of carbon tetrachloride (to eliminate emulsion formation owing to the slight difference in density of the ester and water, compare Methyl Benzoate, Section IV,176) and shake. Separate the lower layer (solution of benzyl acetate in carbon tetrachloride) and discard the upper aqueous layer. Return the lower layer to the funnel, and wash it successively with water, concentrated sodium bicarbonate solution (until effervescence ceases) and water. Dry over 5 g. of anhydrous magnesium sulphate, and distil under normal pressure (Fig. II, 13, 2) with the aid of an air bath (Fig. II, 5, 3). Collect the benzyl acetate a (colourless liquid) at 213-215°. The yield is 16 g. 

This method was later adapted for the large-scale preparation of the LTD4 antagonist 64 by another Merck Process Research group (Figure 3.11) [21], Conversion of a methyl benzoate to the corresponding acetophenone was required. Formation of the tertiary alcohol was again minimized with the addition of H M DS and excellent reaction performance was achieved. 

Many other miscellaneous additions of alcohols have been described. Polar addition of methanol to 2//-pyrroles264 and to azepines265 has been observed. Photoaddition of methanol to the 1,3,4-oxadiazole 320 is followed by cycloelimination of methyl benzoate (321) to give the ylid 322.266 An adduct (323) of the ylid and the 1,3,4-oxadiazole has been isolated. Photoaddition of methanol to the quaternary ammonium salt 324 results in ring expansion and the formation of the azonine 325.267... 

These authors also reported that /V-acyloxy-/V-alkoxyamides did not undergo methanolysis under the same conditions but treatment of /V-acctoxy-/V-ethoxybenz-amide 25a in more forcing conditions with NaOMe in DME afforded a mixture of ethyl and methylbenzoate, 97 and 98 (Scheme 20). They attributed the formation of the former to a HERON reaction and methyl benzoate to the direct attack of methoxide at the amide carbonyl. 

Ethyl formate provides much of the smell of rum and methyl benzoate that for kiwis. I could cite a bunch of additional examples but the point should be clear. 

Amines also react with esters by a method similar to the reaction of an acid chloride with an cimine (which was described in the previous section, From acid chlorides ). Figure 12-28 illustrates the formation of benzamide by this type of reaction, using ammonia and methyl benzoate. Again, the mechanism is similar to the reaction of an acid chloride with an amine (Figure 12-26). 

There is one report of competitive nucleophilic attack at the amide carbonyl in an Ai-acyloxy-A-aUtoxyamide. Shtamburg and coworkers have reported that MeONa reacted with Ai-acetoxy-A-ethoxybenzamide (159) in DME giving methyl and ethyl benzoate (160 and 161) (Scheme 26) . They attributed the formation of methyl benzoate to the direct attack of methoxide ion at the amide carbonyl rather than at nitrogen. The formation of 161 was attributed to a HERON reaction. Though not mentioned by the authors, it seems likely that under these aprotic conditions, 162 could also have been formed by methoxide attack at the acetate carbonyl leading to an anion-induced HERON reaction, by analogy with the reaction of Ai-acyloxy-Ai-alkoxyamides and aqueous hydroxide discussed above (Section IV.C.3.c)... 

There are enthalpies of formation for two phases of cumyl perbenzoate. However, the associated sublimation enthalpy that interconnects these phases, 43 kJ mol , is much too small. In that the enthalpy of sublimation must exceed the enthalpy of vaporization, and the latter is at least 75 kJmol using the CHLP protocol (from the number of carbons alone), the enthalpy of formation data loses credibility. Furthermore, lacking the enthalpy of formation of the corresponding cumyl benzoate (in any phase) disallows comparison. This would seem to be an altogether normal species until it is recognized that the archetype arylcarboxylate ester, methyl benzoate, has provided complications for the calorimetrist . 

When CF3 is allowed to react with methyl benzoate, a new reaction channel appears along with the formation of the carbonyl addition product (Eq. 25). The nucleophile attacks at the methyl group to give an Sn2 substitution with the formation of the benzoate ion. In this case, proton transfer is not possible (no ot hydrogens), but benzoate is a better leaving group than acetate and substitution at the methyl group becomes viable. 

Methyl benzoate, HI, 71, 72 Methyl bromide, HI, 29 Methylene iodide, I, 57-59 Methyl formate, HI, 67 Methyl hexyl carbinol, I, 61-66 Methyl iodide, I, 57, 59 Methyl o-nitrobenzoate, III, 72 Methyl w-nitrobenzoate, HI, 71-72, 73 Methyl Red, II, 47-51... 

The Hammett p-value for cleavage of the exocyclic bond of 2-methoxy-2-substituted-phenyl-l,3-dioxolans (—1.58 + 0.06) is a little larger than that for cleavage of the endocyclic C— bond of 2-hydroxy-2-substituted-phenyl-l,3-dioxolans (—1.24 + 0.04) (Table 9) (Chiang et al., 1983). A direct comparison between the p-values for C—OMe bond cleavage of trimethyl orthobenzoates and dimethyl hemiorthobenzoates is not possible at present since they have not been measured in the same solvent. However, that based on H+ for the breakdown of the hemiorthobenzoates (— 1.58) is less than that based on the equilibrium constants for their conversion into methyl benzoates and methanol which is —1.9 (derived from the equilibrium constants for formation of the hemiorthobenzoates, McClelland and Patel, 1981b). This implies that the development of positive charge in the transition state is less than in the final product, the ester. 

On the other hand, formation of methyl benzoate was also found to occur in methanol, indicating that, together with a general base-catalysis to produce benzamide and with the intramolecular, orthoester mechanism (see p. 110) to give the nitrogenated sugars, a transesterification reaction takes place in which the alkoxide ions play an important role. This can be exemplified by the following sequence. 

Flowery Anisyl alcohol Benzyl acetate, phenylaceiate Cinnamic acid Cinnamyl acetate Citronellyl formate Crcsyl acetate Decanal Dimethyl benzyl carbinol Dimethyl benzyl carbinyl acetate Ethyl anthranilate Geranyl acetate Hydroxycitronellal dimethyl acetate Linalool Linalyl acetate Methyl benzoate Pcnethyl acetate 2-Phcnylpropionaldehyde 3-Phenylpropionaldehvde. 

Fntity Benzyl propionate Butyl acetate Cinnamyl anthranilate. formate Citronellyl acelate. butyrate, isobutyrate. propionate, Delta-decalactone Diethyl malunate Dimethylbenzyl carbinyl acetate Delta-dodecalactone Ethyl p-anlsate. benzoate, butyrate, heptanoate, hexanoate. maltol. nonanoate Isoamyl butyrate, hexanoate. isovalerate, cinnamate Linalyl isobutyrate. propionate Mallol Methyl benzoate, cinnamate 2-Methyl-undecanal, Nerohdol Octanol. Octyl formaie Phencthyl isobuiyrate. isovalerate gamma- Indecalactone. 

A = 12681 CgHgOa C8H.O2 Benzyl Formate Methyl benzoate 203.0 199.4 Nonazeotrope 229... 

A study of gas-phase reactions of benzyl and methoxide anions with alkyl formate and other esters has revealed some differences in behaviour of these anions of comparable basicity.184 The delocalized benzyl anion and localized methoxide ion engage in exclusive transacylation and proton transfer, respectively, on reaction with alkyl formates. However, proton transfer is sufficiently exothermic to dominate when benzyl anion reacts with methyl acetate. Both anions react with methyl benzoate, methyl tiifluoroacetate, and methyl cyanofonnate by competing transacylation and. S n2 reactions. 

Bryce-Smith and Gilbert have shown that toluene, t-butylbenzene, chlorobenzene, o- andp-xylene, and biphenyl all undergo photoaddition to maleic anhydride, yielding 1 2 adducts [33], All the substituents decrease the rate of formation of adducts. Benzonitrile, nitrobenzene, phenol, methyl benzoate, durene, hexamethylbenzene, naphthalene, and biphenylene fail to undergo the addition of these, benzonitrile, nitrobenzene, methyl benzoate, and biphenylene do not form charge-transfer complexes. Bradshaw [34] found that various alkylben-zenes give 1 2 adducts with maleic anhydride upon photosensitization with acetophenone. 

Maleimide also forms 2 1 adducts with acceptor compounds such as benzonitrile, acetophenone, and methyl benzoate [46], This behavior contrasts with that of maleic anhydride, which neither exhibits charge-transfer absorption with nor photoadds to benzenes bearing strong electron-acceptor substituents. It clearly demonstrates that formation of a ground-state charge-transfer complex is not essential in the formation of 2 1 adducts from maleimide and benzene derivatives. 

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